Differences in refractory-period response of canine subendocardium and subepicardium to bunazosin, an alpha1-adrenoceptor antagonist, and propranolol during myocardial ischemia.

Abstract

Our objective was to investigate the effects of alpha1- or beta-adrenoceptor blockers on endocardial and epicardial refractory-period changes during myocardial ischemia in alpha-chloralose-anesthetized dogs. The first and second diagonal branches of the left anterior descending coronary artery were ligated. The refractory period was determined by an S1-S2 extrastimulus method. Dogs were treated with the alpha1-blocker bunazosin (0.1-0.2 mg/kg, i.v.; n = 16), the beta-blocker propranolol (0.2 mg/kg, i.v.; n = 15), or saline (n = 11). Dogs that developed ventricular tachycardia/fibrillation (VT/VF) during the experiment were excluded from the statistical assessment in refractory periods. In all groups, coronary ligation produced a significant shortening of the refractory period of ischemic epicardial tissue (p < 0.05) but only minimal shortening of ischemic endocardial refractory periods, resulting in an increased difference in repolarization time between the endo- and epicardial sites. Treatment with bunazosin ameliorated this ischemia-related shortening of refractory periods at both the endo- and epicardial sites, with a greater effect seen epicardially (p < 0.05), resulting in values similar to those in the nonischemic tissue. Treatment with propranolol prolonged refractory periods more in the epicardial (p < 0.01) than in endocardial sites, exacerbating the disparity in the refractory period between the endo- and epicardial sites (p < 0.05). Propranolol also prolonged the refractory period of nonischemic tissue (p < 0.05 and p < 0.01 in endo- and epicardial sites, respectively), resulting in a significant difference between the ischemic and normal myocardium at the endocardial site (p < 0.05). Results suggest that the alpha1-blocker bunazosin reduces the refractory-period disparity between the ischemic and normal myocardium without increasing the disparity between the endo- and epicardial surfaces, whereas propranolol produces a greater disparity.

• Authors: T Tanabe, K Usui, S Kusuzaki, M Yoshitake, O Takigawa, T Iwamoto, S Handa
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 30 Issue 6 Pg. 824-30 (Dec 1997) ISSN: 0160-2446 [Print] United States
• PMID: 9436824 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-Antagonists
• Adrenergic beta-Antagonists
• Quinazolines
• Receptors, Adrenergic, alpha-1
• bunazosin
• Propranolol

Topics

• Adrenergic alpha-1 Receptor Antagonists
• Adrenergic alpha-Antagonists (pharmacology)
• Adrenergic beta-Antagonists (pharmacology)
• Animals
• Blood Pressure (drug effects)
• Dogs
• Endocardium (drug effects, physiology)
• Heart Ventricles (drug effects)
• Myocardial Ischemia (drug therapy, physiopathology)
• Pericardium (drug effects, physiology)
• Propranolol (pharmacology)
• Quinazolines (pharmacology)
• Receptors, Adrenergic, alpha-1 (metabolism)
• Refractory Period, Electrophysiological (drug effects)
• Tachycardia, Ventricular (prevention & control)
• Ventricular Fibrillation (prevention & control)
• Ventricular Function